Bioavailability is used as a measure of potential efficacy for an orally administered drug. Various factors can affect the bioavailability of orally administered dosage forms. These factors include aqueous solubility, drug absorption, dosage strength, and first pass effect. Aqueous solubility is generally regarded as the main factor that affects bioavailability of HIV protease inhibitors.
Protease inhibitors inhibit cleavage of a protein into peptides. Inhibition of HIV protease is an important approach for the therapeutic intervention in HIV infection. Since the 1990s, these drugs have been a key component of anti-retroviral therapies for HIV/AIDS. One such example of an HIV protease inhibitor is ritonavir.
The state of the art indicates that in order to achieve therapeutically acceptable bioavailability of HIV protease inhibitors, they must be formulated with surfactants; that is, surfactants are critical to achieve therapeutic levels of bioavailability. For example, U.S. Pat. No. 6,599,528 describes a mechanically stable pharmaceutical composition that comprises one or more melt-processable polymers and more than 10% by weight surfactant or a “surface-active substance” in addition to one or more active ingredients that include protease inhibitors. The patent teaches that the improvement in processability is desired when larger amounts of surface-active substances in the range of more than 10% by weight are needed to effectively solubilize the active ingredient.
U.S. Pat. No. 8,399,015 teaches a solid pharmaceutical dosage form comprising a solid dispersion that includes an HIV protease inhibitor (e.g., ritonavir and lopinavir), a pharmaceutically acceptable aqueous-soluble polymer, and a pharmaceutically acceptable surfactant having a hydrophilic-lipophilic balance (HLB) value of from 4 to 10. According to the patent, the inclusion of a surfactant having an HLB value of from 4 to 10 is essential for markedly improving the bioavailability of the HIV protease inhibitor.
U.S. Pat. No. 8,268,349 teaches a solid pharmaceutical dosage form comprising a solid dispersion containing sorbitan monolaurate, at least one pharmaceutically acceptable aqueous-soluble polymer, colloidal silica, and ritonavir.